Drug-metabolism mechanism: Knowledge-based population pharmacokinetic approach for characterizing clobazam drug-drug interactions.

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Tolbert D, Bekersky I, Chu HM, Ette EI

Drug-metabolism mechanism: Knowledge-based population pharmacokinetic approach for characterizing clobazam drug-drug interactions.

J Clin Pharmacol. 2016 Mar;56(3):365-74. doi: 10.1002/jcph.603. Epub 2015 Sep 29.

PubMed ID

26224203 [ View in PubMed

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Abstract

A metabolic mechanism-based characterization of antiepileptic drug-drug interactions (DDIs) with clobazam in patients with Lennox-Gastaut syndrome (LGS) was performed using a population pharmacokinetic (PPK) approach. To characterize potential DDIs with clobazam, pharmacokinetic (PK) data from 153 patients with LGS in study OV-1012 (NCT00518713) and 18 healthy participants in bioavailability study OV-1017 were pooled. Antiepileptic drugs (AEDs) were grouped based on their effects on the cytochrome P450 (CYP) isozymes responsible for the metabolism of clobazam and its metabolite, N-desmethylclobazam (N-CLB): CYP3A inducers (phenobarbital, phenytoin, and carbamazepine), CYP2C19 inducers (valproic acid, phenobarbital, phenytoin, and carbamazepine), or CYP2C19 inhibitors (felbamate, oxcarbazepine). CYP3A4 inducers-which did not affect the oral clearance of clobazam-significantly increased the formation of N-CLB by 9.4%, while CYP2C19 inducers significantly increased the apparent elimination rate of N-CLB by 10.5%, resulting in a negligible net change in the PK of the active metabolite. CYP2C19 inhibitors did not affect N-CLB elimination. Because concomitant use of AEDs that are either CYP450 inhibitors or inducers with clobazam in the treatment of LGS patients had negligible to no effect on clobazam PK in this study, dosage adjustments may not be required for clobazam in the presence of the AEDs investigated here.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Clobazam	Cytochrome P450 2D6	Protein	Humans	No	Inhibitor	Details

Drug Interactions

• Approved
• Vet approved
• Nutraceutical
• Illicit
• Withdrawn
• Investigational
• Experimental
• All Drugs

Drugs	Interaction
Integrate drug-drug interactions in your software
Acebutolol Clobazam	The serum concentration of Acebutolol can be increased when it is combined with Clobazam.
Acetaminophen Clobazam	The serum concentration of Acetaminophen can be increased when it is combined with Clobazam.
Almotriptan Clobazam	The serum concentration of Almotriptan can be increased when it is combined with Clobazam.
Alogliptin Clobazam	The serum concentration of Alogliptin can be increased when it is combined with Clobazam.
Aminophenazone Clobazam	The serum concentration of Aminophenazone can be increased when it is combined with Clobazam.